Cross-sectional studies indicate that Sleep Disordered Breathing (SDB) occurs commonly in individuals with diabetes, hypertension, and obesity, components of the metabolic syndrome. Both causal and non-causal mechanisms may account for these relationships. There have not yet been rigorously conducted studies to assess the extent to which the physiological stressors associated with SDB (i.e., hypoxemia and/or sleep fragmentation) may be causally implicated in metabolic syndrome, and whether treatment of SDB improves indices of the associated insulin resistance. We will test the hypotheses that indices of metabolic syndrome improve more after 2 months of CPAP therapy compared to 2 months of sham-CPAP, and that the magnitude of improvement in indices of metabolic syndrome is associated with the extent of improvement in overnight oxygenation and sleep consolidation. To test these hypotheses, we propose a rigorous controlled assessment of the effect of CPAP (continuous positive airway pressure) therapy on indices of metabolic syndrome, inflammation, and markers of endothelial function. We will exploit the availability of a well-characterized cohort (The Cleveland Family Study) to identify 50 subjects with both SDB and impaired glucose tolerance to participate in an efficacy assessment using a double-blind randomized cross-over CPAP/sham-CPAP intervention. We will apply rigorous clinical trial methodology (run-in and wash-out periods; double-blinding; objective measures of compliance). Data collected at baseline, and after each 2-month intervention period include a comprehensive set of biochemical parameters (measuring glucose metabolism, inflammation, sympathetic activity, coagulation, and oxidative stress), brachial artery ultrasound, and state-of-the-art polysomnography. Abdominal computed tomography will be used to compare visceral fat after each intervention. Euglycemic hyperinsulinemic clamp studies will be performed on a subset of individuals to validate any increase in insulin sensitivity in CPAP-treated participants, and to determine the contribution of changes in the insulin sensitivity of the liver versus peripheral tissues. Demonstration of improved insulin sensitivity with improved sleep quality and overnight oxygenation would provide evidence for a causal role of SDB in the metabolic syndrome, and would provide further support for strategies to screen and treat high risk individuals.